Anatomical location of LPA(1) activation and LPA phospholipid precursors in rodent and human brain

作者：de San Roman Estibaliz Gonzalez; Manuel Ivan; Teresa Giralt Maria; Chun Jerold; Estivill Torrus Guillermo; Rodriguez de Fonseca Fernando; Javier Santin Luis; Ferrer Isidro; Rodriguez Puertas Rafael^*

来源：Journal of Neurochemistry, 2015, 134(3): 471-485.

DOI：10.1111/jnc.13112

• [S-35]GTP gamma S
• brain
• G protein-coupled receptor
• imaging mass spectrometry
• lysophosphatidic acid
• rodent and human

Lysophosphatidic acid (LPA) is a signaling molecule that binds to six known G protein-coupled receptors: LPA(1)-LPA(6). LPA evokes several responses in the CNS, including cortical development and folding, growth of the axonal cone and its retraction process. Those cell processes involve survival, migration, adhesion proliferation, differentiation, and myelination. The anatomical localization of LPA(1) is incompletely understood, particularly with regard to LPA binding. Therefore, we have used functional [S-35]GTPS autoradiography to verify the anatomical distribution of LPA(1) binding sites in adult rodent and human brain. The greatest activity was observed in myelinated areas of the white matter such as corpus callosum, internal capsule and cerebellum. MaLPA(1)-null mice (a variant of LPA(1)-null) lack [S-35]GTPS basal binding in white matter areas, where the LPA(1) receptor is expressed at high levels, suggesting a relevant role of the activity of this receptor in the most myelinated brain areas. In addition, phospholipid precursors of LPA were localized by MALDI-IMS in both rodent and human brain slices identifying numerous species of phosphatides and phosphatidylcholines. Both phosphatides and phosphatidylcholines species represent potential LPA precursors. The anatomical distribution of these precursors in rodent and human brain may indicate a metabolic relationship between LPA and LPA(1) receptors.

• 出版日期2015-8